A major goal of the oral research community is to understand how microbe-microbe and microbe- host interactions affect human health and disease. The proposed research will enable the research community to reach this goal by providing the following research resources: the Human Oral Microbiome Database (HOMD), a web accessible taxonomic and genomic database with oral taxon descriptions and microbiome analysis tools; reference strains for 150 previously uncultured oral bacteria to facilitate in vivo and in vitro experimentation; and genomes for 100 oral taxa that currently lack genetic information. The first Aim will provide and expand a provisional naming scheme (taxonomy) for oral bacteria, including those that have not been formally named or cultivated. HOMD will be expanded to describe over 1,000 human oral taxa, and will incorporate results from the Human Microbiome Projects deep 16S rRNA sequencing of nine oral cavity sites. Completion of this aim will allow investigators to link phenotypic, clinical, genomic and bibliographic information to precisely defined oral taxa based on 16S rRNA sequences. Nearly one-third of the 400 most prevalent oral taxa have no known cultivated isolate and the Second Aim addresses this issue. Such isolates will be identified by 16S rRNA sequencing from the culture collections of investigators Tanner and Wade, and from the collection of L. V. Holdeman Moore and the late Ed Moore, Virginia Polytechnic Institute, now housed at The Forsyth Institute. Targeted isolates for diverse phyla such as TM7, Chlorobi, SR1 and others will be grown in consortia and isolated in pure culture, where possible, using methods we have described. Isolates representing previously uncultivated species will allow investigators to study of in vitro biofilm growth, develop genetic systems, and perform animal model experiments. The Third Aim will obtain genome sequences for 150 oral taxa currently lacking genome information. It will also provide metagenome sequences for oral bacteria that can grow in consortia but not in pure culture. This project will complete the production of reference genomes for nearly all the 400 most prevalent oral bacteria. This information will be a permanent resource for interpretation of metagenome data, for the production of microarrays for transcriptome studies, and for generating protein fragment libraries from genomic coding for proteomic studies. The genome information, tool, and strains generated by this project will serve as a permanent foundation and resource for investigations on the role of the oral microbiome in human health and disease.